Immune Therapy Offers Hope in Ovarian Cancer

by Michael Smith Michael Smith North American Correspondent, MedPage Today
April 07, 2013

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Note that this study was published as an abstract and presented at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.

A novel two-step immunotherapy process appears to be effective in nearly three-fourths of women with advanced ovarian cancer when combined with chemotherapy.

The process begins with treatment with a personalized vaccine derived from the patient's own dendritic cells and is followed by a second step, called adoptive T-cell therapy, in which immune cells are reinjected into patients after being removed, stimulated, and expanded in the laboratory.

WASHINGTON -- A novel two-step immunotherapy process appears to be effective in nearly three-fourths of women with advanced ovarian cancer, a researcher said here.

The process begins with treatment with a personalized vaccine derived from the patient's own dendritic cells, according to Lana Kandalaft, PharmD, PhD, of the University of Pennsylvania.

In 65% of 31 patients in a small nonrandomized trial, the vaccine alone led to either stable disease or partial response, Kandalaft told reporters at the annual meeting of the American Association for Cancer Research.

A subset of 11 patients went on to the second step of the process -- called adoptive T-cell therapy -- and 73% had what Kandalaft called a "clinical benefit" -- either stable disease or a shrinking of the tumor.

Most patients with advanced ovarian cancer relapse within 2 years, she noted, and most die within 5 years. "There is definitely a vast unmet need for the development of novel, alternate therapies," she said.

The process appears to offer new hope for patients with recurrent, progressive ovarian cancer, Kandalaft said, adding that some participants in the trial have had stable disease for several months.

Indeed, she said one woman, who had relapsed twice and had undergone three debulking surgeries before being given the dendritic cell vaccine, has now had 45 months of progression-free survival.

"To this day, she's still in quite good condition," she said.

The role of dendritic cells, she noted, is to act as "spies" -- collecting information about potential targets and bringing the data back to the T cells, the "soldiers" that kill those targets.

In the study, Kandalaft and colleagues kept participants' tumor cells alive after debulking surgery and then isolated dendritic cells through apheresis. The cells were exposed to tumor antigens and then injected into patients' lymph nodes, along with intravenous bevacizumab (Avastin), over about 3 months.

In 20 of 31 patients, Kandalaft reported, the vaccine alone led to clinical benefit -- 17 patients had stable disease and three had a partial response. The vaccination was well tolerated and elicited tumor-specific T-cell responses against various ovarian tumor antigens, with some patients experiencing prolonged progression-free survival.

The 11 patients who went on to the second stage of the process had their T cells removed, stimulated and expanded in the lab, and replaced in large numbers. The transfer amplified the antitumor immune response, Kandalaft reported, because the T cells had already been educated by the dendritic cell vaccine to attack tumor cells.

Of the 11 participants in the second stage, seven had stable disease and one had a complete remission, she said.

The study "shows that it's now possible to devise very efficient and complex but feasible combination strategies (starting with) a vaccination that will basically point the immune system in the direction of the tumor," commented Louis Weiner, MD, of Georgetown University here, who was not part of the study.

"And then you can further expand that response in a very productive and useful way through an adoptive transfer of activated T cells that have been educated to attack that particular set of antigens," he told reporters.

Such a combination approach, he said, has the potential to "overcome some of the innate resistance mechanisms that cancers use."

The study had support from the National Cancer Institute, the National Institutes of Health, and the Ovarian Cancer Immunotherapy Initiative. Kandalaft made no disclosures.

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